1. Field of the Invention
The present invention relates to an agent for reducing nephrotoxicity due to a platinum complex compound, particularly cisplatin, comprising an activated spherical carbon as an active ingredient, the use of an activated spherical carbon for reducing nephrotoxicity due to a platinum complex compound, particularly cisplatin, and a method of reducing nephrotoxicity due to a platinum complex compound, particularly cisplatin, comprising administering an effective amount of activated spherical carbon.
2. Description of the Related Art
Recently, chemotherapy for a cancer has rapidly progressed. Nevertheless, an antitumor agent acts not only on tumorous tissues, but also on normal tissues. Thus, adverse effects are inevitable. Therefore, there are many attempts to reduce the adverse effects.
Platinum complex compounds, particularly cisplatin, i.e., cis-dichloro-diamine-platinum, are excellent antitumor agents. A remarkable prolongation of life can be expected in testicular tumor, bladder cancer, pyeloureter tumor, kidney cancer, prostatic cancer, or ovarian cancer by administering such a compound. Main adverse effects of cisplatin are nephrotoxicity, gastrointestinal disorder, hemotoxicity, and neurotoxicity. In particular, the nephrotoxicity is the major dose-limiting adverse effect in a usual intravenous, intraarterial or intraperitoneal administration.
The nephrotoxicity is caused by cisplatin secreted in uriniferous tubules. The longer the high concentration of cisplatin is maintained, the severer nephropathy is caused. The degree of nephropathy may be determined by means of, for example, creatinine clearance. Sometimes, a severe symptom, such as renal insufficiency, is caused.
Cisplatin is generally administered under the diuretic condition. It is managed to reduce the nephrotoxicity by lowering the concentration of cisplatin in uriniferous tubules. The diuretic condition may be produced by adding water and administering diuretic agent, such as mannitol or furosemide. It is also known that systemic adverse effects due to cisplatin administration can be reduced, using a hemoperfusion column charged with activated carbon, in combination therewith. Feun et al. disclosed experiments wherein activated charcoals were orally administered to dogs after the intravenous administration of cisplatin to the dogs (Proc. Am. Assoc. Cancer Res., 1985, vol. 26, No. 1039).
Japanese Unexamined Patent Publication (Kokai) No. 6-192109 enumerates sodium thiosulfate, acetazolamide, selenium dioxide, sodium selenate, cysteine, 3-aminobenzamide, fosfomycin, S-adenosy-L-methionine and so on, as compounds which can reduce the nephrotoxicity due to cisplatin.
However, the administration under the diuretic condition or the combined use of the hemoperfusion column charged with activated carbon inflicts a pain on a patient, and the nephrotoxicity was not satisfactorily reduced. The Feun et al. reference only discloses the prolongation effect of life, but does not disclose the reduction of the nephrotoxicity. Of the compounds enumerated in said Japanese publication, no compound has been put to clinical use. Therefore, there was a desire to develop an agent for definitely reducing the nephrotoxicity caused by cisplatin administration.